UBC Theses and Dissertations
The effect of d-govadine on conditioned place preference with d-amphetamine or food reward Nesbit, Maya
Pharmacological treatments for drug addiction often relate to the dopamine (DA) system, which is known to play a key role in the development, persistence and relapse to compulsive drug-taking. However, many agents that alter single-receptor DA signaling have been clinically ineffective and there is growing interest in compounds targeting multiple receptors as a more promising therapeutic approach. Tetrahydroprotoberberines (THPB) derived from traditional Chinese herbal medicines have a high affinity for DA D1 and D2 receptors and have potential as novel treatments for drug addiction. This study assessed the effects of the THPB d-govadine on the acquisition, maintenance, expression and reinstatement of amphetamine-induced conditioned place preference (CPP). Furthermore, the effect of d-govadine on the acquisition and maintenance of food CPP was evaluated to gain insight into its action on multiple forms of reward-learning. Amphetamine CPP was established in rats by pairing d-amphetamine (1.5 mg/kg, i.p.) or saline with compartments with distinct contextual cues, and food CPP was induced by pairing Froot loops or no Froot loops with distinct contexts. In separate experiments, rats received d-govadine (0.5, or 1.0 mg/kg, i.p.) or vehicle, a) before each d-amphetamine injection during the conditioning phase, b) before tests for expression of amphetamine-induced CPP, c) before amphetamine-induced reinstatement of CPP, or d) before placement into food-associated compartments during the conditioning phase. CPP was assessed as greater time spent in the amphetamine- as compared to saline-paired contexts. d-govadine did not affect the acquisition of amphetamine CPP. However, groups that were pre-treated with d-govadine dose-dependently extinguished their preference for the amphetamine-associated context at a faster rate compared to vehicle-treated animals. While the expression of amphetamine CPP was not affected by d-govadine administered on the test day, the amphetamine-induced reinstatement of CPP following an extinction period was blocked by d-govadine (1.0 mg/kg). Finally, the intermediate dose of d-govadine (0.5 mg/kg) blocked the acquisition of food CPP and rats pre-treated with the high dose (1.0 mg/kg) extinguished their preference at a faster rate than vehicle-treated animals. These data suggest that d-govadine affects the acquisition of reward-context associations and the ability of amphetamine to reinstate preference for the amphetamine-associated compartment.
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